Streptococcus suis type 2 PPCDC protein affects permeability of blood-brain barrier

Abstract:

[Background] Streptococcus suis type 2 (SS2) is a major zoonotic pathogen leading to global economic and public health problems, causing meningitis, arthritis, and sepsis. Phosphopantothenoylcysteine decarboxylase (PPCDC) was screened out in the previous study about the interaction between the porcine blood-brain barrier model in vitro and S. suis genome-wide phage display random library, while the mechanism of PPCDC in affecting the blood-brain barrier remains unclear. [Objective] To explore the role of PPCDC in the SS2-induced meningitis. [Methods] In this study, the recombinant protein rPPCDC was expressed in Escherichia coli. The monolayer barrier model of human brain microvascular endothelial cells in vitro and the mouse infection model in vivo were established to study the effect of rPPCDC on the permeability of blood-brain barrier. Furthermore, the rPPCDC vaccine was prepared for the immunoprotection test in mice. [Results] The soluble recombinant protein rPPCDC was successfully purified. This protein reduced the transmembrane resistance of cells in the monolayer barrier model, increased the number of SS2 breaking through the monolayer barrier in vitro. In addition, the protein enhanced the pathogenicity of SS2 in mice. The mice vaccinated with rPPCDC had higher serum levels of rPPCDC antibodies and increased survival. [Conclusion] PPCDC can enhance the permeability of blood-brain barrier and promote the destruction of blood-brain barrier and brain infection of SS2 in mice, thus exerting the immunoprotective effect. The findings provide new ideas for the future research on the pathogenic mechanism of SS2 and the development of vaccines.

Key words:Streptococcus suis type 2;PPCDC;blood-brain barrier;immunoprotection